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Super bacterial infection caused by metallo‐β‐lactamases (MβLs) has posed a serious public health threat, while developing inhibitors of MβLs is an ideal strategy to combat drug‐resistance. Here, seventeen sulfonylureas were synthesized and confirmed. Biological assay shown that these molecules effectively inhibited MβL ImiS, with an IC50 value in the range of 29.5–188.2 μM, and the best inhibitor competitively and irreversibly inhibited ImiS with a Ki value of 15.2 μM. Structure‐activity relationship analysis revealed that the chlorine‐substituted phenyl significantly raised inhibitory activity of sulfonylureas on ImiS. Antibacterial and chessboard dilution assays shown that the most sulfonylureas tested enhanced antimicrobial effect of meropenem (MER) on E. coli‐ImiS, and the two inhibitors with best effect resulted in an 8‐fold reduction in MIC of MER. Mice tests shown that the best inhibitor synergizing MER virtually diminished the load of E. coli‐ImiS in spleen and liver. Docking study revealed that the sulfonylurea reacts with ImiS mainly through the sulfonyl group, in which one of oxygen atoms coordinates to Zn(II), and forms two hydrogen bonds with Lys224 (2.1 Å) and His263 (3.1 Å). This work revealed the sulfonylureas are promising candidates for the development of ImiS inhibitors. [ABSTRACT FROM AUTHOR]

This work describes a phase-transformation pathway of calcium phosphate in the presence of glutamic acid. The route follows the order starting from amorphous calcium phosphate and brushite, then octacalcium phosphate (OCP), and finally hydroxyapatite (HAp). The preferred growth direction of the intermediate OCP and the final HAp phases lies along the c axis. On the basis of our scanning electron microscopy, X-ray powder diffraction, and [sup.31]P solid-state NMR data, we suggest that the transformation is via the dissolution-reprecipitation process, which is facilitated in the presence of glutamic acid. The effect on the transformation kinetics is rationalized by the disruption of the water layer bound on the crystal surface. Key words: biomineralization, octacalcium phosphate, calcium phosphate, HAp, NMR. Dans ce travail, on decrit une voie de transformation de phase du phosphate de calcium en presence d'acide glutamique. Cette voie suit un ordre partant du phosphate de calcium amorphe et de la brushite et passant par le phosphate d'octacalcium (POC) pour arriver finalement a l'hydroxyapatite (HAp). La direction de croissance preferee des phases du POC intermediaire et de l' hydroxyapatite finale se trouve le long de l' axe c. Sur la base des donnees de microscopie electronique a balayage, de diffraction des rayons-X par des poudres et de RMN du [sup.31]Pal'etat solide, on suggere que la transformation se produit par le biais d'un processus de dissolution-reprecipitation qui est facilite par la presence d'acide glutamique. L'effet sur la cinetique de la transformation est rationalise par la rupture de la couche d'eau liee a la surface cristalline. Mots-cles : Biomineralisation, phosphate d'octacalcium, phosphate de calcium, hydroxyapatite (HAp), RMN. [Traduit par la Redaction], Introduction Biomineralization processes mainly occur at an organic-inorganic interface with the mediation of various biomolecules. However, questions of how these biomolecules control nucleation, growth, and morphology of inorganic minerals remain [...]

Self-designed reverse electric field electrospinning device and non-solution contact electrospinning device were employed to carry out a series of electrospinning experiments, and ANSYS finite element analysis software was used to simulate and analyze the field intensity distributions of the electrospinning setups, and thus to demonstrate the feasibility of non-solution contact electrostatic spinning technology theoretically and practically. The research results showed that, by using non-solution contact electrospinning technology, the nanofibers with narrow diameter distribution can also be obtained and no residual solvent, meanwhile the morphology of the nanofibers were same to that from conventional electrospinning technology, and the former has excellent safety property, which is expected to realize the production of nanofibers at industrial scale. [ABSTRACT FROM AUTHOR]

A liquid chromatography-tandem mass spectrometry method was established and validated for determining the concentrations of costunolide(CO), piperine(PI), agarotetrol(AG), glycyrrhizic acid(GL), vanillic acid(VA), and glycyrrhetinic acid(GA) in rat plasma. This method was then applied to the toxicokinetic study of these six compounds in rats with chronic cerebral ischemia(CCI) following multiple oral doses of Zhachong Shisanwei Pills. Finally, the effects of continuous multiple-dose administration of Zhachong Shisanwei Pills on the liver of CCI rats were investigated. The results showed that after oral administration of different doses of Zhachong Shisanwei Pills, the in vivo exposure of AG, VA, and GA was relatively high, with AUC_(0-∞) values ranging from 604.0-2 494.2, 1 305.4-4 634.5, and 2 177.5-4 045.7 h·ng·mL~(-1), respectively, while the exposure of CO, PI, and GL was relatively low, with AUC_(0-∞) values ranging from 37.8-238.2, 2.4-17.0, and 146.9-408.5 h·ng·mL~(-1), respectively. The C_(max) and AUC_(0-∞) of the six compounds were positively correlated with the administered dose. The T_(max) of PI and AG ranged from 0.3 to 2.0 h, their T_(1/2) ranged from 0.8 to 2.9 h, and their mean residence time(MRT) ranged from 1.0 to 3.7 h. The T_(max) of GL and VA was shorter(0.4-1.9 h), while their T_(1/2)(2.6-5.9 h) and MRT(2.5-8.5 h) were longer. Both CO and GA exhibited a bimodal phenomenon, with T_(max) ranging from 1.6 to 6.6 h, T_(1/2) ranging from 2.8 to 7.7 h, and MRT ranging from 4.1 to 12.9 h. Liver histopathology after 28 days of continuous multiple-dose administration of Zhachong Shisanwei Pills showed that the liver tissue remained normal at a low dose(crude drug 0.8 g·kg~(-1), approximately 5 times the clinical equivalent dose). However, as the dose increased(crude drug 1.1-3.0 g·kg~(-1), 6.9-18.8 times the clinical equivalent dose), varying degrees of liver damage were observed. Blood biochemical tests revealed no significant changes in the serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid(TBA) in CCI rats from administration groups 1 to 3(crude drug 0.8, 1.1, 1.5 g·kg~(-1)). However, ALT, AST, ALP, and TBA levels in groups 4 and 5(crude drug 2.1, 3.0 g·kg~(-1)) showed significant increases. This study preliminarily elucidated the toxicokinetic characteristics of the six compounds in Zhachong Shisanwei Pills and their effects on liver tissue in CCI rats, providing data as a reference for clinical use.

Objective: To investigate DNA repair in CHL cells and HeLa cells after DNA damage induced by different oxidative agents., Methods: CHL cells and HeLa cells were exposed to various damaging agents, CHL cells: H(2)O(2) for 25 min, K(2)Cr(2)O(7) for 105 min, doxorubicin (Dox) for 75 min HeLa cells: H(2)O(2) for 25 min, K(2)Cr(2)O(7) for 105 min; then cells were continuously cultured for 0-3 h after washing. Alkaline single cell gel electrophoresis (ASCGE) assay was used to detect DNA strand breaks., Result: (1) DNA strand breaks were induced in CHL cells after exposure to H(2)O(2) K(2)Cr(2)O(7) or Dox, which were repaired evidently after continuous culture for 1 h(P<0.01). The damages induced by H(2)O(2) or K(2)Cr(2)O(7) were repaired completely after culture for 2-3 h. However, the demage induced by Dox was repaired incompletely. (2) DNA strand breaks were induced also in HeLa cells after exposure to H(2)O(2) or K(2)Cr(2)O(7), which were repaired evidently after continuous culture for 0.5 h(P<0.01),and completely after culture for 1 h. (3) The regression coefficient related to the rate of comet cells and repair time was statistically different (P<0.05) between CHL cells and HeLa cells., Conclusion: DNA damage induced by Dox is repaired more difficult than that induced by H(2)O(2) or K(2)Cr(2)O(7). The repair initiates immediately after DNA damage in both of cells, but more rapidly in HeLa cells than in CHL cells.